Zeitgeber

Abstract: Melatonin is a ubiquitous molecule and widely distributed in nature, with functional activity occurring in unicellular organisms, plants, fungi and animals. In most vertebrates, including humans, melatonin is synthesized primarily in the pineal gland and is regulated by the environmental light/dark cycle via the suprachiasmatic nucleus. Pinealocytes function as 'neuroendocrine transducers' to secrete melatonin during the dark phase of the light/dark cycle and, consequently, melatonin is often called the 'hormone of darkness'. Melatonin is principally secreted at night and is centrally involved in sleep regulation, as well as in a number of other cyclical bodily activities. Melatonin is exclusively involved in signaling the 'time of day' and 'time of year' (hence considered to help both clock and calendar functions) to all tissues and is thus considered to be the body's chronological pacemaker or 'Zeitgeber'. Synthesis of melatonin also occurs in other areas of the body, including the retina, the gastrointestinal tract, skin, bone marrow and in lymphocytes, from which it may influence other physiological functions through paracrine signaling. Melatonin has also been extracted from the seeds and leaves of a number of plants and its concentration in some of this material is several orders of magnitude higher than its night-time plasma value in humans. Melatonin participates in diverse physiological functions. In addition to its timekeeping functions, melatonin is an effective antioxidant which scavenges free radicals and up-regulates several antioxidant enzymes. It also has a strong antiapoptotic signaling function, an effect which it exerts even during ischemia. Melatonin's cytoprotective properties have practical implications in the treatment of neurodegenerative diseases. Melatonin also has immune-enhancing and oncostatic properties. Its 'chronobiotic' properties have been shown to have value in treating various circadian rhythm sleep disorders, such as jet lag or shift-work sleep disorder. Melatonin acting as an 'internal sleep facilitator' promotes sleep, and melatonin's sleep-facilitating properties have been found to be useful for treating insomnia symptoms in elderly and depressive patients. A recently introduced melatonin analog, agomelatine, is also efficient for the treatment of major depressive disorder and bipolar affective disorder. Melatonin's role as a 'photoperiodic molecule' in seasonal reproduction has been established in photoperiodic species, although its regulatory influence in humans remains under investigation. Taken together, this evidence implicates melatonin in a broad range of effects with a significant regulatory influence over many of the body's physiological functions.

Abstract: 1 Introduction.- 1.1. The Circadian System.- 1.2. Human Circadian Rhythms.- 1.3. Operations and Methods.- 1.3.1. Facilities and Subjects.- 1.3.2. The Measurements.- 1.3.3. The Analyses.- 2 Autonomous Rhythms.- 2.1. External Synchronization and Desynchronization.- 2.1.1. Free Running Rhythms.- 2.1.2. Criteria for Autonomy.- 2.1.3. Criteria for Oscillatory Origin.- 2.1.4. Application of the Criteria to Critical Experiments.- 2.1.5. Summary of Free Running Rhythms.- 2.2. Internal Synchronization and Desynchronization.- 2.2.1. Real Internal Desynchronization.- 2.2.2. Apparent Internal Desynchronization.- 2.2.3. Internal Dissociation.- 2.2.4. Internal Desynchronization: Other Indications.- 2.2.5. Conclusions.- 2.3. Review of Autonomous Rhythms.- 2.4. External Modifications of Autonomous Rhythms.- 2.4.1. Influence of Light Intensity.- 2.4.2. Influence of Light Modality.- 2.4.3. Influence of Ambient Temperature.- 2.4.4. Influence of Natural Electromagnetic Fields.- 2.4.5. Influence of Artificial Electromagnetic Fields.- 2.4.6. Influence of Physical Workload.- 2.4.7. Influence of Psychical Burden.- 2.4.8. Influence of Social Contacts.- 2.4.9. Summary.- 3 Heteronomous Rhythms.- 3.1. General Effects of External Zeitgebers.- 3.1.1. Alterations of the Zeitgeber Period.- 3.1.2. Shifts of the Zeitgeber Phase.- 3.1.3. Entrained versus Free Running Rhythms.- 3.2. Modalities of Effective Zeitgebers.- 3.2.1. Light-dark Zeitgebers.- 3.2.2. Physical versus Social Zeitgebers.- 3.2.3. Electric Field Zeitgebers.- 3.2.4. Summary.- 3.3. Partial Synchronization.- 3.3.1. Strong Light-dark Zeitgebers.- 3.3.2. External Modifications of Partially Desynchronized Rhythms.- 3.3.3. Experiments with Continuously Changing Zeitgeber Period.- 3.3.4. Review of Partially Synchronized Rhythms.- 3.4. General Effectiveness of Light-dark Zeitgebers.- 3.5. General Mode of Zeitgeber Action.- 4 Synthesis.- 4.1. The One Oscillator Model.- 4.1.1. Autonomous Rhythms.- 4.1.2. Entrained Rhythms.- 4.1.3. Conclusions.- 4.2. The Multioscillator Model.- 4.2.1. Internal Dissociation.- 4.2.2. Internal Desynchronization.- 4.2.3. Properties of Separated Oscillators.- 4.3. Internal Interaction Between Different Rhythms.- 4.3.1. Oscillatory Interaction.- 4.3.2. Reactive Interactions.- 4.3.3. Separation of the Interactions.- 5 Conclusions and Speculations.- 5.1. Theoretical Aspects.- 5.2. Practical Aspects.- 5.2.1. Problems of Phase Maps.- 5.2.2. Problems of Rhythm Disorders.- 6 References.- Author Index.

Abstract: Sleep-wake rhythm disturbances in patients with Alzheimer's disease (AD) make a strong demand on caregivers and are among the most important reasons for institutionalization. Several previous studies reported that the disturbances improve with increased environmental light, which, through the retinohypothalamic tract, activates the suprachiasmatic nucleus (SCN), the biological clock of the brain. The data of recently published positive and negative reports on the effect of bright light on actigraphically assessed rest-activity rhythms in demented elderly were reanalyzed using several statistical procedures. It was demonstrated that the light-induced improvement in coupling of the rest-activity rhythm to the environmental zeitgeber of bright light is better detected using nonparametric procedures. Cosinor, complex demodulation, and Lomb-Scargle periodogram-derived variables are much less sensitive to this effect because of the highly nonsinusoidal waveform of the rest-activity rhythm. Guidelines for analyses of actigraphic data are given to improve the sensitivity to treatment effects in future studies.